👤 W Strobl

Apolipoprotein A-V (apoAV) contributes to the regulation of triglyceride metabolism, which plays a role in the pathogenesis of atherosclerotic diseases. We therefore ascertained determinants of hepatic APOA5 transcript and apoAV plasma levels in humans. We determined influences of anthropometric variables, biochemical factors related to lipid and glucose metabolism, hepatic mRNA levels transcribed from the APOA1/C3/A4/A5 cluster and transcription factor genes implicated in the regulation of APOA5 as well as common single nucleotide polymorphisms (SNPs) at the APOA5 locus on APOA5 expression in 89 obese patients and 22 non-obese controls. Mean, age and sex adjusted, hepatic APOA5 mRNA or apoAV plasma levels did not differ by obesity status, homoeostasis model assessment insulin resistance or inflammatory markers. In multivariate regression models, the c56C > G SNP, plasma apoCIII, plasma nonesterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels. Hepatic transcript levels of carnitine palmitoyltransferase 1 (CPT1A1) and peroxisome proliferator-activated receptor alpha (PPARA), plasma nonesterified fatty acids and the c56C > G SNP explained 48% of the variance in hepatic APOA5 transcript levels. Apolipoprotein A-V plasma levels are independently associated with plasma free fatty acid and hepatic APOA5 mRNA levels. Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism. Show less

Apolipoprotein AV (apoAV) is a recently discovered apolipoprotein with a triglyceride-lowering effect in genetically modified mice. Transcription of the human gene encoding apoAV (APOA5) is suppressed by insulin and stimulated by fibrates. Our goal was to study the expression of Apoa5, in comparison with Apoa4 and Apoc3, in hypertriglyceridaemic, obese and insulin-resistant Zucker rats receiving the insulin sensitiser rosiglitazone and/or a fish oil diet to lower triglycerides. Hepatic Apoa5, Apoa4 and Apo3 mRNA and liver and plasma apoAV were measured in lean and obese Zucker rats receiving rosiglitazone while on a coconut oil or fish oil diet. Basal hepatic Apoa5 expression was similar in obese and lean Zucker rats. Unexpectedly, obese Zucker rats tended to have higher plasma apoAV levels despite their hypertriglyceridaemic state. Both rosiglitazone and the fish oil diet significantly increased Apoa5 mRNA, by about 70%, but tended to lower liver and plasma apoAV. Rosiglitazone had no effect on Apoa5 mRNA in cultured rat hepatocytes. No intact PPAR (peroxisome proliferator-activated receptor) response element was identified in the rat Apoa5 promoter. Our data indicate that apoAV does not contribute to the hypertriglyceridaemia of obese Zucker rats or to the hypolipidaemic effect of rosiglitazone or a fish oil diet. The divergent changes of Apoa5 mRNA and apoAV levels suggest co- or post-translational regulation. The increase in Apoa5 mRNA induced by rosiglitazone is not directly mediated by peroxisome proliferator-activated receptor gamma. Show less

Apolipoprotein (apo) A-IV is an antiatherogenic apolipoprotein, which may be involved in the regulation of food intake. Plasma apoA-IV is elevated in human obesity and apoA-IV polymorphisms have been associated with the extent of obesity. Our aim was to determine the effects of weight loss on plasma apo-IV in obese adolescents and to examine the relation of apoA-IV with the degree of obesity. Longitudinal intervention study of a low fat hypocaloric diet conducted in a dietary camp. Two groups of obese adolescents (n=47 and n=29), age: 12.7+/-1.7 and 11.7+/-2.6 y, relative body mass index (RBMI): 168+/-24 and 175+/-34%, respectively. Plasma total apoA-IV, apoA-I, apoB, plasma distribution of apoA-IV, leptin, lipids, and lipoproteins before and after 3 weeks of weight reduction. Plasma apoA-IV decreased from 11.5+/-4.1 mg/dl before to 6.7+/-2.2 mg/dl after weight reduction in the first group (P<0.001) and to a similar extent in the second group. The relative amount of lipid-free apoA-IV and apoA-IV associated with apoA-I increased slightly, whereas apoA-IV associated with lipoproteins devoid of apoA-I decreased. ApoA-IV levels before and after weight reduction and the changes in plasma apoA-IV did not independently correlate with RBMI, weight loss, or plasma leptin. Plasma apoA-IV decreases markedly in overweight adolescents undergoing short-term weight reduction. The decrease is not directly related to the degree of weight loss and the mechanisms underlying this reduction remain to be clarified. Show less